The broad, long term objective of the proposed research is to develop Fourier domain (FD) functional optical coherence tomography (F-OCT) and spectral domain (SD) second harmonic OCT (SH-OCT) instruments that can image tissue structure and physiology with high imaging speed and sensitivity, high spatial resolution, and high contrast. OCT is a promising noninvasive, noncontact imaging modality that uses coherence gating to obtain cross-sectional images of tissue microstructure with micrometer resolution. Doppler, polarization sensitive (PS), and second harmonic OCT are important functional extensions of OCT that enhance OCT contrast and provide cross-sectional mapping of physiological relevant information such as tissue microcirculation, birefringence, and nonlinear optical properties. There are many clinical conditions where determination of tissue structure, blood flow, birefringence, and nonlinear optical properties provide important diagnostic and therapeutic information. However, most functional extensions of OCT currently use the time domain method, which has limited speed and sensitivity. We propose to develop a swept source based FD F-OCT and a spectrometer based SD SH-OCT that can provide microscopic tissue morphology and multiple physiological parameters with high imaging speed and sensitivity. The specific aims of this work are to: (1) Design and develop a swept source-based FD F-OCT system that provides Doppler and polarization capability with high speed 2-D and 3-D imaging capability, (2) Design and develop a SD SH-OCT system with high sensitivity, (3) Test and optimize FD SH-OCT and demonstrate in clinical studies how FD F-OCT can assist in the optimal management of patients where imaging tissue structure, blood flow, and birefringence are important, and (4) Test and optimize SD SH-OCT and demonstrate in animal model studies how SD SH-OCT can assist in imaging and quantifying oral dysplasia and malignancy. The proposed research will significantly increase the diagnostic potential of in vivo OCT imaging technology. Although this proposal focuses only on burn depth diagnosis and oral cancer detection, the technology developed will have a broad impact in clinical applications of OCT technology including, but not limited to, diagnosis and management of ocular pathologies, cardiaovascular diseases, and cancers in gastrointestinal, respiratory, and urogenital tracts.